Award Ceremony Speech

Why do children resemble their parents? This question has
probably always fascinated humans, but not until the advent of
natural science have we arrived at an increasingly satisfactory
answer.

In the middle of the last century, the
Austrian monk Gregor Mendel conducted his famous breeding
experiments with the garden pea. He concluded that every trait of
an individual plant is determined by a set of two genes, one
obtained from each parental plant. To Mendel a gene was an
abstract concept, which he used to interpret his breeding
experiments. He had no idea of the physical properties of
genes.

Only in the mid-1940s could it be
established that in terms of chemistry, genetic material is
composed of the nucleic acid DNA. About ten years later the
double helical structure of DNA was revealed. Ever since then,
progress within the field of molecular biology has been very
rapid, and several Nobel prizes have been awarded in this area of
research.

Initially, genetic material was studied
mainly in simple organisms, particularly in bacteria and
bacterial viruses. It was shown that a gene occurs in the form of
a single continuous segment of the long, thread-like DNA, and it
was generally assumed that the genes in all organisms looked this
way. Therefore, it was a scientific sensation when this year's
Nobel Laureates, Richard Roberts and Phillip Sharp, in 1977,
independently of each other, observed that a gene in higher
organisms could be present in the genetic material as several
distinct and separate segments. Such a gene resembles a mosaic.
Both Roberts and Sharp analyzed an upper respiratory virus, which
is particularly suitable for studies of the genetic material in
complex organisms. It soon became apparent that most genes in
higher organisms, including ourselves, exhibited this mosaic
structure.

Roberts' and Sharp's discovery opened up a
new perspective on evolution, that is, on how simple organisms
develop into more complex ones. Earlier it was believed that
genes evolve mainly through the accumulation of small discrete
changes in the genetic material. But their mosaic gene structure
also permits higher organisms to restructure genes in another,
more efficient way. This is because during the course of
evolution, gene segments - the individual pieces of the mosaic -
are regrouped in the genetic material, which creates new mosaic
patterns and hence new genes. This reshuffling process presumably
explains the rapid evolution of higher organisms.

Roberts and Sharp also predicted that a
specific genetic mechanism is required to enable split genes to
direct the synthesis of proteins and thereby to determine the
properties of the cell. Researchers had known for many years that
a gene contains detailed instructions on how to build a protein.
This instruction is first copied from DNA to another type of
nucleic acid, known as messenger RNA. Subsequently, the RNA
instruction is read, and the protein is synthesized. What Roberts
and Sharp were now stating was that the messenger RNA in higher
organisms has to be edited. The required process, called
splicing, resembles the work that a film editor performs: the
unedited film is scrutinized, the superfluous parts are cut out
and the remaining ones are joined to form the completed film.
Messenger RNA treated in this manner contains only those parts
that match the gene segments. It later turned out that the same
parts of the original messenger RNA are not always saved during
the editing- there are choices. This implies that splicing can
regulate the function of the genetic material in a previously
unknown way.

Roberts' and Sharp's discovery also helps
us understand how diseases arise. One example is a form of anemia
called thalassemia, which is due to inherited defects in the
genetic material. Several of these defects cause errors in the
editing process during splicing; thus, an abnormal messenger RNA
is formed and subsequently also a protein that functions poorly
or not at all.

The discovery of split genes was
revolutionary, triggering an explosion of new scientific
contributions. Today this discovery is of fundamental importance
for research in biology as well as in medicine.

Dr. Richard Roberts and Dr. Phillip
Sharp,

Your discovery of split genes led to the prediction of a new
genetic process, that of RNA splicing. The discovery also changed
our view of how genes in higher organisms develop during
evolution. On behalf of the Nobel Assembly of the Karolinska
Institute I wish to convey to you our warmest congratulations,
and I now ask you to step forward to receive the Nobel Prize from
the hands of His Majesty the King.